Normal and neoplastic lymphocytes have surface membrane receptors for immunoglobulin. Receptors which are heavy chain class specific have been demonstrated with respect to IgG, IgM and IgA. In our preliminary experiments, we have shown that B lymphocytes will bind normal and neoplastic fluorescent labelled aggregated IgM and IgA. Utilizing these reagents, Ig receptors were sought on lymphoma-leukemia cells. Our results suggest that there may be correspondence between the heavy chain class specificity of surface membrane immunoglobulin and the corresponding immunoglobulin Fc receptor. By implication, therefore, one can construct a model of B cell differentiation involving a series of heavy chain specific immunoglobulin synthetic shifts corresponding to different levels of differentiation. Likewise, human lymphoid neoplasms which are generally B cell derived may be subdivided into potentially clinically useful subgroups according to these phenotypic markers. We propose to study B cell differentiation pathways with respect to Ig receptors and SmIg in order to (1) characterize B cell differentiation, (2) delineate clinically important subgroups of patients with lymphoid malignancies who have differing prognoses based on marker phenotype. In order to do so, we will utilize 2 model systems. The first is a normal neonatal mouse spleen model which will provide information regarding the ontogeny of B lymphocyte receptors during fetal development. The second is the study of human lymphoid neoplasms. Fluorescent labelled reagents will be utilized and cells viewed under fluorescence microscopy. Cells will also be analyzed and sorted by the fluorescent activated cell sorter (FACS IV), particularly double fluorescent labelled cells. Heavy chain specific EA (Ig) complexes will be used to compare to the results obtained with Ig aggregates. Clinical information derived from patients with neoplasms studied for Ig receptors will be analyzed to determine whether there are differences in survival, response to treatment or other clinical paramaters which correspond to differing phenotypic profiles.